increased detrusor collagen is associated with detrusor overactivity and decreased bladder compliance in men with benign prostatic obstruction

Accepted Manuscript Increased Detrusor Collagen is Associated with Detrusor Overactivity and Decreased Bladder Compliance in Men with Benign Prostatic Obstruction Carlos Henrique Suzuki Bellucci, Wesley de Oliveira Ribeiro, Thiago Souto Hemerly, José de Bessa, Jr., Alberto Azoubel Antunes, Katia Ramos Moreira Leite, Homero Bruschini, Miguel Srougi, Cristiano Mendes Gomes PII: S2287-8882(16)30018-6 DOI: 10.1016/j.prnil.2017.01.008 Reference: PRNIL 84 To appear in: Prostate International Received Date: May 2016 Revised Date: December 2016 Accepted Date: 18 January 2017 Please cite this article as: Suzuki Bellucci CH, de Oliveira Ribeiro W, Hemerly TS, de Bessa J Jr., Antunes AA, Leite KRM, Bruschini H, Srougi M, Gomes CM, Increased Detrusor Collagen is Associated with Detrusor Overactivity and Decreased Bladder Compliance in Men with Benign Prostatic Obstruction, Prostate International (2017), doi: 10.1016/j.prnil.2017.01.008 This is a PDF file of an unedited manuscript that has been accepted for publication As a service to our customers we are providing this early version of the manuscript The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain ACCEPTED MANUSCRIPT INCREASED DETRUSOR COLLAGEN IS ASSOCIATED WITH DETRUSOR OVERACTIVITY AND DECREASED BLADDER COMPLIANCE IN MEN WITH BENIGN PROSTATIC RI PT OBSTRUCTION Carlos Henrique Suzuki Bellucci, Wesley de Oliveira Ribeiro, Thiago Souto Hemerly, José de Bessa Jr., Alberto Azoubel Antunes, Katia Ramos Moreira Leite, Homero SC Bruschini, Miguel Srougi, Cristiano Mendes Gomes M AN U Division of Urology, University of Sao Paulo School of Medicine, Sao Paulo, Brazil TE D Running Head: Detrusor collagen content in prostatic obstruction Number of Figures: Number of Tables: AC C EP Manuscript word count: 2590 Key Words: prostatic hyperplasia, urinary bladder, collagen, smooth muscle, urodynamics ACCEPTED MANUSCRIPT Abstract Purpose: To investigate the relationship between detrusor collagen content and urodynamic parameters in men with benign prostatic obstruction Material and Methods: Nineteen consecutive patients undergoing open prostatectomy RI PT for bladder outlet obstruction due to benign prostatic hyperplasia (BOO/BPH) were evaluated Urodynamic was performed in all patients BOO and detrusor contractility were assessed with the BOO index (BOOI) and the bladder contractility index (BCI), SC respectively A bladder fragment was obtained during prostatectomy Eight cadaveric organ donors composed the control group Bladder sections were stained with M AN U Picrosirius Red and hematoxilin-eosin The collagen to smooth muscle ratio (C/M) in the detrusor was measured and its relationship with urodynamic parameters was investigated Results: Seven (36.8%) patients were operated due to lower urinary tract symptoms and TE D twelve (63.2%) were in urinary retention Mean prostate volume was 128.6 ± 32.3 cm3 Mean BOOI of 76.4 ± 33.0 and a mean BCI of 116.1 ± 33.7 Mean C/M in BPH patients and controls were 0.43 ± 0.13 and 0.33 ± 0.09, respectively (p = 0.042) A negative EP correlation was shown between C/M and bladder compliance (r= - 0.488, p=0.043) The C/M was increased in BPH patients with detrusor overactivity (DO) compared to those AC C without DO (0.490 ± 0.110 and 0.360 ± 0.130, respectively; p=0.030) and also in patients in urinary retention (p=0.002) No correlation was shown between C/M and maximum cystometric capacity, BOOI or BCI Conclusions: Men with BOO/BPH have increased detrusor collagen content which is associated with decreased bladder compliance, detrusor overactivity and urinary retention ACCEPTED MANUSCRIPT Introduction Benign prostatic hyperplasia (BPH) is a common disease in aged men and is often associated with prostate enlargement and lower urinary tract symptoms (LUTS/BPH).1 Bladder outlet obstruction (BOO) has long been considered a key factor in the RI PT mechanism through which BPH causes LUTS and the relief of obstruction is the traditional basis of most therapies developed for the treatment of LUTS/BPH.1 However, LUTS/BPH not consistently correlate with parameters used for evaluating SC BOO, such as prostate volume, urinary flow, postvoid residual urine and even pressureflow parameters.2 In addition, the mechanism through which storage phase symptoms M AN U develop in men with LUTS/BPH is unclear and many patients undergoing surgical treatment for LUTS/BPH persist with storage symptoms after relief of BOO.3, In order to investigate the complex pathophysiology of LUTS/BPH, researchers have turned their attention to bladder abnormalities and evidences support a major role for detrusor TE D muscle abnormalities in the development of LUTS/BPH.5 Bladder outlet obstruction induces morphophysiological changes in the bladder that may result in bladder dysfunction, including detrusor overactivity, detrusor EP underactivity and decreased compliance.6, Men with BOO due to BPH (BOO/BPH) may develop detrusor hypertrophy and hyperplasia and accumulation of connective AC C tissue within the muscle bundles.8, If, on one hand, detrusor abnormalities can be regarded as a consequence of BOO, on the other hand, morphologic and functional abnormalities of the bladder can possibly have a direct role in determining LUTS/BPH.5 Studies including men with BOO/BPH have shown increased collagen content in the detrusor.9-11 It has also been suggested that the magnitude of detrusor collagen deposition is associated with the severity of LUTS in men with BOO/BPH.10 Nevertheless, the interrelationship between detrusor collagen content and functional ACCEPTED MANUSCRIPT parameters, such as bladder capacity, detrusor overactivity, compliance, severity of obstruction and detrusor contractility is poorly understood In the present study, we investigated the correlation between detrusor collagen content and urodynamic AC C EP TE D M AN U SC RI PT parameters in men with BOO/BPH ACCEPTED MANUSCRIPT Patients and Methods Over a period of 12 months, 19 patients (median age 69 years, range 62 to 81) undergoing open prostatectomy for BPH were enrolled in the study Exclusion criteria were previous history of pelvic, bladder or prostate surgery, previous pelvic RI PT radiotherapy, prostate or bladder cancer, presence of bladder stones, urethral stricture and neurological diseases with possible impact on the lower urinary tract This study was approved by the Institutional Review Board of our hospital Patients agreed to SC participate after full disclosure of its purposes and written consent was obtained from all participants M AN U All patients underwent a comprehensive evaluation including a focused urological history, International Prostate Symptom Score (IPSS), physical examination including digital rectal examination, prostatic specific antigen level (PSA), urine analyses and culture and transabdominal sonography for evaluation of the kidneys, bladder, prostate TE D volume and postvoid residual urine All patients underwent urodynamics and definitions are in accordance with the International Continence Society terminology.12 The urodynamic parameters evaluated were maximum cystometric capacity, bladder EP compliance, presence of detrusor overactivity, maximum flow rate during pressure/flow study and detrusor pressure in the maximum flow rate Detrusor overactivity (DO) was AC C defined as any involuntary detrusor contraction during the filling phase Detrusor contractility was assessed with the bladder contractility index (BCI) and was considered normal if greater than 100.13 Bladder outlet obstruction was assessed with the bladder outlet obstruction index (BOOI) and was considered obstructed if BOOI>40 and unobstructed if BOOI